title: Emodin and [6]-gingerol lessen hypoxia-induced embryotoxicities in cultured mouse whole embryos via upregulation of hypoxia-inducible factor 1α and intracellular superoxide dismutases.
abstract: Excess hypoxia during embryonic organogenesis leads to developmental abnormalities and postnatal deficits. To determine whether emodin and [6]-gingerol affects hypoxia-induced anomalies during embryonic organogenesis, we cultured embryonic day 8.5 mouse embryos under hypoxic conditions (5% O(2)) for 2 days with or without emodin (1 × 10(-8) μg/mL), [6]-gingerol (1 × 10(-9) μg/mL), and SOD mimetics MnTBAP (1 × 10(2) nM/mL) and then investigated the developmental changes and expression patterns of hypoxia-inducible factor 1α (HIF-1α), cytoplasmic superoxide dismutase (SOD1), and mitochondrial SOD (SOD2) in the embryos. Hypoxic conditions induced various developmental anomalies in the growth stages and remarkably low levels of HIF-1α, SOD1 and SOD2 mRNAs, and SOD activity in the embryos; however, these effects were significantly reversed by treatment with emodin, [6]-gingerol, and MnTBAP, respectively. Our findings indicate that antioxidants such as emodin, [6]-gingerol, and MnTBAP lessen hypoxia-induced embryotoxicities via upregulation of HIF-1α and intracellular SODs.
authors.affiliation: College of Veterinary Medicine and Research Institute of Veterinary Medicine Priority Research Institute of NRF, Chungbuk National University, Cheongju 361-763, South Korea.
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Yon
authors.forename: In-Jeoung
authors.initials: IJ
authors.lastname: Baek
authors.forename: Beom Jun
authors.initials: BJ
authors.lastname: Lee
authors.forename: Young Won
authors.initials: YW
authors.lastname: Yun
authors.forename: Sang-Yoon
authors.initials: SY
authors.lastname: Nam
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology*; D015687:Cell Hypoxia; D019610:Cytoprotection; D046149:Embryo Culture Techniques; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004642:Emodin / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005865:Gestational Age; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D015854:Up-Regulation; D000099156:Superoxide Dismutase 2
chemical_list: D000975:Antioxidants; D002396:Catechols; D004642:Emodin; D005233:Fatty Alcohols; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008665:Metalloporphyrins; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C497443:Hif1a protein, mouse; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; C007845:gingerol; C000606291:Sod1 protein, mouse